In recent years, ES cell (Embryonic Stem cell) and iPS cell (induced Pluripotent Stem cell) which have ability of differentiation into various tissue cells of human body (hereinafter, referred to as “pluripotency”) were discovered, and research and development have been carried out on a technology for putting such ES cell and iPS cell to practical use in drug design field, medical transplantation field, etc. ES cell and iPS cell (hereinafter, collectively referred to as “the pluripotent stem cell”) are a type of cell that can be artificially established from an egg cell or a somatic cell, and have ability to differentiate ex vivo into various tissue cells and to self-renew infinitely, i.e. to be grown and divided into two cells, one of which is a differentiated cell and another is a cell of the same type as before.
In the drug design field, the pluripotent stem cell is induced and differentiated from a human somatic cell into a hepatic cell or a cardiac muscle cell, for example, in order to evaluate hepato-toxicity or cardio-toxicity of candidate drug compounds. In the medical transplantation field, the pluripotent stem cell is induced and differentiated from a human somatic cell into a retina cell, a cornea cell, a nerve cell, a dopaminergic cell, an insulin-secreting cell, a cardiac muscle cell, a hepatic cell, etc., in order to supply a source for cell transplantation therapy. Particularly, iPS cell can be induced from an individual somatic cell of any person, whose personality has been found, by a gene-recombination operation, and hence is expected to supply the source of transplantation therapy using autologous iPS cell, i.e. iPS cell established from a somatic cell of a patient who is going to have the transplantation therapy, which will eliminate or reduce the need for immunosuppressive drug owing to prevention of transplant rejection.
In order to put the drug design and the transplantation therapy with the pluripotent stem cell to practical use, there is a need for a cell culture facility in which the pluripotent stem cell can be mass-produced or mass-cultured as differentiating into various tissue cells or without differentiation. In the conventional cell culture facility, stepwise cleanliness control zones are formed, and a cell culture room is arranged in a sterile control zone (clean-room) whose pressure difference is controlled to the surroundings, for culturing cells while securing sterility of products. In order to effectively culture a great amount of cells necessary for the medical transplantation therapy etc., the facility is proposed that a plurality of cell culture rooms are arranged in a sterile control zone (refer to Patent Document Nos 1 to 3). It is also possible to culture a great amount of cells automatically, for example, by arranging an automatic cell culturing apparatus in each of the cell culture rooms in the facility.
Furthermore, when supplying a cell sheet for heart transplantation therapy using the pluripotent stem cell, for example, it is necessary to combine more than one culturing steps, such as a step of growing the undifferentiated pluripotent stem cell, a step of differentiating the stem cell into a particular tissue cell, e.g. a muscle myoblast cell or a cardiac muscle cell, a step of growing the differentiated pluripotent stem cell to prepare a monolayer-cell sheet, a step of stacking a plurality of the cell sheets, etc. If respective culturing steps is carried out in a different culture room, a vast sterile control zone is required in the conventional facility, and cleanliness control in the facility is complicated. A system called “isolator” has been developed to solve the problem, with which each culturing step can be carried out in respective sealed spaces in the system (refer to Patent Document Nos 4 and 5). Using the conventional facility (as described in Patent Document Nos 1 to 3) where a plurality of the isolator (as described in Patent Document Nos 4 and 5) are arranged in respective culture rooms, a great amount of pluripotent stem cell can be cultured by carrying out each of the culturing steps in respective sealed spaces in the isolators, while minimizing the sterile control zone in the facility, resulting in simplifying the cleanliness control in the facility and reducing the operator's support which may causes contamination of the products.